Development of Novel Methods for Chemical Modification ofEndogenous Proteins in Living Cells

摘要

Chemical modification of proteins provides powerful tools to realize a broad range ofexciting biological applications,including the development of new classes ofbiopharmaceuticals and functional studies of individual proteins in complex biologicalsystems.Numerous strategies for linking desired chemical probes with target proteins havebeen developed in the last two decades,with most exploiting genetic protein engineeringand/or bio-orthogonal chemistry that utilizes unnatural amino acids incorporated intoproteins.1 On the other hand,modification of endogenous (native) proteins in biologicalcrude environments by site-specific and target-selective approaches remains challengingbecause appropriate organic chemistry to carry out such modifications is currently limited.To realize chemical modification and functionalization of endogenous cellular proteins,ourgroup has developed several methods based on affinity labeling techniques.Furthermore,we succeeded in developing an organelle protein selective labeling method by preciselycontrolling the subcellular distribution of reactive chemical compounds.This presentationwill cover our three strategies for chemical modification of endogenous proteins in livingcells.